Recently attention has again become directed to the endocrine pancreas as the site of the lesion responsible for human diabetes mellitus. The observation that the numbers of beta cells are significantly reduced in diabetes calls attention to the need for gaining insight into the natural history of the beta cell, and for delineating the mechanisms which control beta cell neogenesis. The objectives of this study are: (1) to obtain an integrated view of the biochemistry, physiology and morphology of the beta cell from the prenatal period through full maturity, with specific emphasis on the factors which regulate new beta cell formation; and (2) to explore the feasibility of utilizing implantation of beta cells grown in tissue culture as a means for treating diabetes. The experimental models to be utilized include in vivo studies in diabetic mutant (C57 BL/Ks-dbdb) mice and subhuman primates. In addition, tissue culture techniques will be used both for implantation studies and to examine beta cells from rodents and primates under controlled in vitro conditions for extended periods of time. Islet cell morphology and beta cell replication will be examined by light and electron microscopy and by radioautography following tritiated thymidine. Insulin biosynthesis will be examined using labeled amino acid precursors and column chromatography and insulin secretion using the double antibody immunoassay technique.